Yu Tzu Chang

Handgrip strength is an independent predictor of renal outcomes in patients with chronic kidney diseases

BACKGROUNDnIn dialysis patients, protein-energy wasting (PEW) is associated with high mortality, and some indicators of PEW, such as serum albumin value, subjective global assessment (SGA) score and handgrip strength (HGS), may predict mortality. However, whether PEW is associated with poor renal outcomes and whether the indicators of PEW can predict renal outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD-ND) is still unclear.nnnMETHODSnWe enrolled 128 clinically stable patients with CKD-ND and followed up for 33.8 ± 9.2 months. Baseline characteristics, echocardiographic information, laboratory data, HGS, SGA scores, anthropometric parameters, bioimpedance analyses and other indicators of PEW were examined in relation to the risk of reaching renal composite end points of pre-dialysis mortality or dialysis-dependent end-stage renal disease.nnnRESULTSnTwenty-six patients reached composite renal end points. Multivariate Cox regression analyses showed that HGS was an independent predictor of renal outcome in patients with CKD-ND of Stages 1-5 [CKD(1-5), hazard ratio (HR) = 0.90, P = 0.004] or advanced CKD-ND of Stages 3b [defined as estimated glomerular filtration rate (eGFR) of 30-44 mL/min/1.73 m(2)] to 5 (CKD(3b-5), HR = 0.91, P = 0.031), but not serum albumin, SGA score or other indicators of PEW. When the cutoffs were set at 24.65 kg in men with CKD(1-5), 20.15 kg in men with CKD(3b-5) and 10.15 kg in women with CKD(1-5) or CKD(3b-5), which were deduced from receiver-operating characteristics analyses, patients with lower HGS had significantly poor renal outcomes in Kaplan-Meier survival analyses in all subgroups and higher HR for reaching renal end points in multivariate Cox regression analyses in all subgroups except for women with CKD(3b-5), whose HR had marginal significance (HR = 3.78, P = 0.068) after adjusting for age and eGFR.nnnCONCLUSIONSnThis is the first study demonstrating that HGS is an independent predictor of composite renal outcomes in CKD-ND patients. HGS can be incorporated to clinical practice for assessing nutrition status and renal prognosis in patients with CKD-ND.

Inhibiting glycogen synthase kinase-3 reduces endotoxaemic acute renal failure by down-regulating inflammation and renal cell apoptosis

Background and purpose:u2002 Excessive inflammation and apoptosis are pathological features of endotoxaemic acute renal failure. Activation of glycogen synthase kinase‐3 (GSK‐3) is involved in inflammation and apoptosis. We investigated the effects of inhibiting GSK‐3 on lipopolysaccharide (LPS)‐induced acute renal failure, nuclear factor‐κB (NF‐κB), inflammation and apoptosis.

Increased Aortic Stiffness and Attenuated Lysyl Oxidase Activity in Obesity

Objective—One potential mechanism through which obesity exerts adverse effects on the vascular system is by increasing aortic stiffness, a change known to be predictive of increased cardiovascular mortality. The aim of this study was to investigate the pathophysiology that links obesity to aortic stiffening. Approach and Results—Obese (ob/ob) mice were used to examine physical, morphological, and molecular changes in the aorta in response to obesity. ob/ob mice had increased aortic pulse wave velocity and tissue rigidity. ob/ob aorta exhibited decreases of lysyl oxidase (LOX) activity and cross-linked elastin, and increases of elastin fragmentation and elastolytic activity. The aortas of ob/ob mice were surrounded by a significant amount of proinflammatory and pro-oxidative perivascular adipose tissue. In vitro studies revealed that the conditioned medium from differentiated adipocytes or the perivascular adipose tissue of ob/ob mice attenuated LOX activity. Furthermore, inhibition of LOX in wild-type lean mice caused elastin fragmentation and induced a significant increase in pulse wave velocity. Finally, we found that obese humans had stiffer arteries and lower serum LOX levels than do normal-weight humans. Conclusion—Our results demonstrated that obesity resulted in aortic stiffening in both humans and mice, and established a causal relationship between LOX downregulation and aortic stiffening in obesity.

Diabetes and End-Stage Renal Disease Synergistically Contribute to Increased Incidence of Cardiovascular Events: A Nationwide Follow-up Study During 1998–2009

OBJECTIVE This study aimed to investigate the effect of interaction of diabetes and end-stage renal disease (ESRD) on the risks of cardiovascular (CV) events. RESEARCH DESIGN AND METHODS By using two representative national cohorts, we determined the age- and sex-specific incidences and 20-year risks of incident CV events, including acute myocardial infarction (AMI), stroke, and congestive heart failure (CHF), stratified by the presence of diabetes, de novo diabetes after ESRD, or ESRD. Individuals were excluded if age <18 years or if previous CV events or malignancies were present before enrollment. Cox proportional hazards models were also constructed with adjustments for competing risk of mortality. RESULTS A total 648,851 non-ESRD individuals and 71,397 ESRD patients, including 53,342 and 34,754 diabetic patients, respectively, were followed up during 1998–2009. A monotonic risk pattern of CV-related incidences was noted with the presence of diabetes, ESRD, or both, respectively, after stratification by age and sex. De novo diabetes showed similar increased risks for CV incidences, especially AMI and stroke. There is a multiplicatively synergistic effect of diabetes and ESRD for CV-related risks, especially for AMI and stroke, of which the adjusted hazard ratios (aHRs) were 5.24 (95% CI 4.83–5.68) and 2.43 (2.32–2.55), respectively, in comparison with people without diabetes or ESRD; de novo diabetes after ESRD had similar effects with aHRs of 4.12 (3.49–4.87) and 1.75 (1.57–1.95), respectively. CONCLUSIONS Diabetes and ESRD synergistically increase risks of CV events. Proactive screening and control for diabetes in patients with ESRD should be built into our daily practice.

Poor immune response to a standard single dose non-adjuvanted vaccination against 2009 pandemic H1N1 influenza virus A in the adult and elder hemodialysis patients

BACKGROUNDnHemodialysis patients have higher risk of mortality and morbidity when infected with 2009 pandemic H1N1 (pH1N1/09) virus. Depending on different methodologies and criteria, previous studies reported variable response rates to adjuvanted vaccines against pH1N1/09 virus in hemodialysis patients, however, the efficacy of non-adjuvanted vaccines, which are currently used in many countries such as the USA and Asian areas, has not been comprehensively evaluated in hemodialysis population before.nnnMETHODSnWe evaluated the efficacy of a standard single 15 μg-dose of non-adjuvanted monovalent pH1N1/09 vaccine (AdimFlu-S) in vaccine-naïve 110 hemodialysis and 173 healthy participants. When enrolling, all participants had not any clinical symptom or sign suggesting pH1N1/09 infection since the index case was identified in Taiwan. Sera from all participants were tested by hemagglutination inhibition (HI) and micro-neutralization-ELISA (microNT-ELISA) tests before and 21 days after vaccination. The outcome parameters were seroconversion rate (≥ 4-fold in HI titer with titer ≥ 1:40), seroprotection rate (HI titers ≥ 1:40), seroresponse rate (≥ 4-fold increase in HI or microNT-ELISA titer), fold of increase in geometric mean (GM) titers, and adverse effects.nnnRESULTSnIn method A analyses, we included all participants data in final analyses, and the seroconversion rates and the fold increase of GM titer after vaccination were 25.4% and 1.8 in adult (18-60-year olds) hemodialysis subgroup, and 23.4% and 1.8 in elder (>60-year olds) hemodialysis subgroup based on HI titers, which were all significantly lower than those of the corresponding healthy control subgroups. Similar trends were observed based on microNT-ELISA titers, further validating the results. Multivariable analysis revealed hemoglobin and cholesterol levels were significant predictors for seroresponse in hemodialysis patients, suggesting the possible impacts of nutrition status and anemia. In method B analyses, we excluded participants with pre-vaccination seroprotection (based on HI or microNT-ELISA criteria) in final analyses. The response rates in various subgroups from method B analyses were also similar as those from method A analyses. No severe adverse effect was noted.nnnCONCLUSIONSnAccording to the European and U.S. criteria, a single 15 μg-dose of non-adjuvanted pH1N1/09 vaccination is safe but ineffective in both adult and elder hemodialysis patients. Further studies using multiple doses or higher antigen amount are warrant to define the most appropriate regimen.

Associations between arsenic in drinking water and the progression of chronic kidney disease: A nationwide study in Taiwan

To evaluate the associations between exposure to arsenic in drinking water and the progression of chronic kidney disease (CKD), we conducted a study in Taiwan. We recruited 8854 participants from a nationwide health screening program from 2000 to 2009 who were at least 20 years old and had two checkups in a 24-month period with at least 12 months apart. We defined CKD as having an estimated glomerular filtration rate (eGFR)<90ml/min/1.73m2 or renal dysfunction demonstrated by proteinuria and a rapid progression of CKD as a decline in eGFR>5ml/min/1.73m2/year. Arsenic levels were assessed on the basis of a governmental nationwide survey. Of the 8854 participants, 1341 exhibited rapid progression. Participants who lived in areas with arsenic levels≥50μg/L had a higher risk of rapid progression, with an odds ratio of 1.22 (95% confidence interval: 1.05-1.42, p<0.01) after adjusting for hypertension, diabetes mellitus, proteinuria, and anemia. The results showed that a high arsenic level in drinking water was a risk factor for rapid progression of CKD, independent of most of the documented risk factors. Screening and intervention programs should be implemented in endemic areas of exposure to reduce the risk.

Estimation of Physical Functional Disabilities and Long-term Care Needs for Patients Under Maintenance Hemodialysis

Background and Objectives:Physical functional disabilities in hemodialysis (HD) patients may increase their mortality and long-term care needs. The aim of this study was to estimate the changes of proportion for different physical functional disabilities along time after beginning HD and the lifelong care needs. Methods:We used a population-based cohort consisting of 84,657 incident HD patients in Taiwan between 1998 and 2009 to estimate the survival function and extrapolate to lifetime through a semiparametric method. The Barthel Index (BI) was used to measure the functional disability levels cross-sectionally in 1334 HD patients recruited from 9 HD centers. A BI score <50 was considered as severe disability. Lifetime care needs were obtained by extrapolating the age-stratified survival functions to lifetime and then multiplying them with proportions of different kinds of functional disabilities over time. Results:On average, HD patients had at least 6.4, 2.0, and 1.3 years without disability, with moderate disability, and severe disability, respectively. The most common care needs were stair-climbing and bathing, which were 3.0 and 1.7 years, respectively. HD patients were expected to have about 3 years living with disabilities for those beginning HD at an age above 35 years; however, the older the patient, the higher the proportion of functional disabilities and care needs. Conclusions:HD patients are in need of long-term care and require early intervention and resource planning. The method developed in this study can also be applied to other chronic illnesses with various functional disabilities.

Parathyroidectomy Associates with Reduced Mortality in Taiwanese Dialysis Patients with Hyperparathyroidism: Evidence for the Controversy of Current Guidelines

Parathyroidectomy is recommended by the clinical guidelines for dialysis patients with unremitting secondary hyperparathyroidism (SHPT). However, the survival advantage of parathyroidectomy is debated because of the selection bias in previous studies. To minimize potential bias in the present nationwide cohort study, we enrolled only dialysis patients who had undergone radionuclide parathyroid scanning to ensure all patients had severe SHPT. The parathyroidectomized patients were matched with the controls based on propensity score for parathyroidectomy. Mortality hazard was estimated using multivariate Cox proportional hazard models adjusting for comorbidities before scanning (model 1) or over the whole study period (model 2). Our results showed that among the 2786 enrolled patients, 1707 underwent parathyroidectomy, and the other 1079 were controls. The crude mortality rates were lower in the parathyroidectomized patients than in the controls. In adjusted analyses for the population matched on propensity score, parathyroidectomy was associated with a significant 20% to 25% lower risk for all-cause mortality (model 1: hazard ratio 0.76, 95% confidence interval 0.61 to 0.94; model 2: hazard ratio 0.80, 95% confidence internal 0.64 to 0.98). We concluded that parathyroidectomy was associated with a reduced long-term mortality risk in dialysis patients with severe SHPT.

Elevated Serum Interleukin-18 Level Is Associated with All-Cause Mortality in Stable Hemodialysis Patients Independently of Cardiac Dysfunction

Background High circulating interleukin (IL)-18 level predicts a higher hospitalization rate among dialysis patients, possibly through cardiovascular mechanisms; however, whether higher IL-18 level is associated with mortality in dialysis patients is less clear. In addition, its impacts on left ventricular (LV) function are also unknown. We conducted a cohort study to examine the impacts of IL-18 level on LV function and prognosis among clinically stable hemodialysis patients. Methods Clinically stable patients undergoing maintenance hemodialysis (≥3 months) were prospectively enrolled from December 2008 to January 2009, and were followed up for 31 months. The enrolled patients (41% male, 66.4±10.9 years of age) received 2-dimensional echocardiography and myocardial deformation (strain) analysis, including LV peak systolic longitudinal strain (GLS) and circumferential strain (CS). Laboratory measurements were also performed. Cox regression analysis was used to investigate prognostic factors. Results Seventy-five patients were stratified into 2 groups by the median value of IL-18 (654.2 pg/ml). Between these 2 groups, there was no significant difference in baseline characteristics including LV ejection fraction. The high IL-18 group had a worse LV systolic function as demonstrated by reduced GLS and CS. Seventeen patients (22.7%) died during the follow-up period. Multivariate Cox regression analysis showed that low serum albumin, the presence of hypertension, high serum IL-18, and less negative GLS (>−15%) were independently associated with all-cause mortality. No significant interaction between IL-18 and less negative GLS was noted in the final Cox model. Conclusion Hemodialysis patients with high IL-18 levels tend to have worse LV systolic function and higher mortality rate. However, elevated serum IL-18 level is predictive of poor prognosis among stable hemodialysis patients, independently of LV dysfunction. This suggests an additional value of IL-18 to echocardiographic study in predicting all-cause mortality, and IL-18 may be helpful in early risk stratification of hemodialysis patients.

Cost-effectiveness of hemodialysis and peritoneal dialysis: A national cohort study with 14 years follow-up and matched for comorbidities and propensity score

Although treatment for the dialysis population is resource intensive, a cost-effectiveness analysis comparing hemodialysis (HD) and peritoneal dialysis (PD) by matched pairs is still lacking. After matching for clinical characteristics and propensity scores, we identified 4,285 pairs of incident HD and PD patients from a Taiwanese national cohort during 1998–2010. Survival and healthcare expenditure were calculated by data of 14-year follow-up and subsequently extrapolated to lifetime estimates under the assumption of constant excess hazard. We performed a cross-sectional EQ–5D survey on 179 matched pairs of prevalent HD and PD patients of varying dialysis vintages from 12 dialysis units. The product of survival probability and the mean utility value at each time point (dialysis vintage) were summed up throughout lifetime to obtain the quality-adjusted life expectancy (QALE). The results revealed the estimated life expectancy between HD and PD were nearly equal (19.11 versus 19.08 years). The QALE’s were also similar, whereas average lifetime healthcare costs were higher in HD than PD (237,795 versus 204,442 USD) and the cost-effectiveness ratios for PD and HD were 13,681 and 16,643 USD per quality-adjusted life year, respectively. In conclusion, PD is more cost-effective than HD, of which the major determinants were the costs for the dialysis modality and its associated complications.